The FUS about familial amyotrophic lateral sclerosis

The debilitating neurologic disease familial amyotrophic lateral sclerosis (FALS), commonly known a Lou Gehrig’s disease, has been linked to mutations in several different genes, including the gene encoding the DNA/RNA binding protein FUS. Haiyan Qiu, Sebum Lee and colleagues developed a transgenic mouse model of FUS-associated FALS to examine how mutated FUS promotes FALS pathogenesis. FUS-R521C mice exhibited phenotypes similar to patients, including neurological dysfunction and pronounced DNA damage. The authors identified the brain-derived neurotrophic factor (Bdnf), a nerve growth factor that promotes dendritic growth and synaptic function, as a target of mutant FUS. Treatment of FUS-R521C neurons with BNDF only partially restored dendrite function, suggesting that FUS-R521C disrupts other factors required for neuron function. Evaluation of spinal cords from FUS-R521C revealed that there were multiple defects in the transcription and splicing of genes associated with dendrite growth and function as well as genes required for immune regulation. The accompanying image uses Golgi's method of silver impregnation to highlight the reduced dendritic arborization in the spinal motor neurons of a 1 month-old FUS-R521C transgenic mouse.